textile slow-release systems with medical applications · the growth in medical knowledge has also...

AUTEX Research Journal, Vol. 2, No4, December 2002 © AUTEX

http://www.autexrj.org/No6/0043.pdf

TEXTILE SLOW-RELEASE SYSTEMS WITH MEDICALAPPLICATIONS

M.R. ten Breteler, V.A. Nierstrasz and M.M.C.G. Warmoeskerken

Textile TechnologyDepartment of Chemical TechnologyUniversity of TwenteP.O. Box 2177500 AE EnschedeThe Netherlands

E-mail: [email protected]

Abstract

In the development of medical drug delivery systems, attention has been increasingly focused onslow- or controlled delivery systems in order to achieve an optimal therapeutic effect. Since theadministration of drugs often requires a defined or minimum effective dosage in the human body,more conventional delivery systems such as tablets require relatively high doses, which can resultin undesired toxic effects. Subsequent degradation of the drug in the human body will result in adrug concentration below the minimum effective level. Furthermore, there are situations where oraladministration is less advisable, such as in cases of prolonged treatment or with people that areforgetful, which again results in ineffective treatment. Textile slow-release systems have thepotential to overcome these negative aspects. Drugs containing transdermal patches for ex-vivoapplications are already familiar; however, this paper will not deal with such applications, but withmore advanced in-vivo textile slow-release systems. Due to enormous progress over the years inthe fields of supramolecular chemistry, nanotechnology, and polymer science & technology, anumber of promising drug delivery technologies have been developed. This review will focus onthe opportunities of textiles bearing cyclodextrins, aza-crown ethers or fullerenes, as well as ion-exchange fibres, drug-loaded hollow fibres, textiles treated with nanoparticles and fibres withbioactive compounds in their embodiment. In this paper, the delivery systems will be discussedand compared in terms of biostability, biodegradability, controllability, toxicity, carcinogenicity,interface reactions, material costs and the fabrication process.

Keywords: slow release systems, drug delivery, medical, cyclodextrins, aza-crown ethers,fullerenes, ion-exchange fibres, hollow fibres, nanoparticles, entrapment, encapsulation.

Introduction

Over the years, people have always tried to improve the quality and length of life, and with success.Positive developments in hygiene and nutrition have increased the average lifespan by several years.The growth in medical knowledge has also greatly contributed to this, and developments are stillongoing. Besides searching for solutions to medical problems, many attempts have been made toimprove the comfort of application. Textile systems can be useful in this respect.A specific aspect within the medical field is the delivery of drugs. Pills, ointments, injections andsuchlike are already familiar; though these are useful in many cases, situations can be thought of inwhich other systems would be more applicable. In oral delivery systems (e.g. tablets, pills, capsules),the drug is absorbed in the stomach or intestinal tract [1, 2]. As some drugs become metabolised,either there or in the liver, they lose their efficacy before being able to fulfil their medical purpose.Consequently, relatively high doses are necessary to achieve an effect, which might give rise to livertoxic metabolites [1, 2]. Delivery through the skin circumvents the liver passage, allowing drugdosages to be reduced. Ointments are an alternative, but only for those therapeutic agents that willgive no side effects in case of overdose [1]. Moreover, there are situations where oral administration isless applicable or impractical, e.g. with children, people with swallowing difficulties or people who areforgetful, for example because of dementia. Transdermal (through the skin) and in-vivo (inside the

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body) drug delivery systems constitute a good alternative in these situations. Finally, with prolongeddrug treatment, these systems are more preferable than daily injections or intake of pills.One general benefit obtained from the use of textile materials is protection. Over the years, wearingcomfort and the quality of textiles have improved, and textile materials now form an important aspectof our everyday lives. Besides the material itself, the structure is important. While dependent on thefabrication process, textile materials are often permeable, breathing structures, and usually treated tohave an absorptive capacity. Therefore, textile materials have also found applications in the medicalfield. Their ‘breathing’ capability especially makes textile materials a useful basis for ex-vivo (outsidethe body) applications. Moreover, as people are used to wearing textile materials, it seems logical toexamine these materials as a possible basis for drug delivery systems.Over the years, a number of delivery methods have been developed. So-called transdermal patchesare already familiar. Most such patches consist of multi-layer systems, in which in addition to anointment (or other drug-containing substance), a regulatory system (e.g. a membrane) is used. Thispaper will not discuss these kinds of systems, but will essentially focus on the following promisingsystems:• textiles bearing cyclodextrins;• textiles bearing aza-crown ethers;• textiles bearing fullerenes;• ion-exchange fibres;• drug-loaded hollow fibres;• textiles treated with nanoparticles;• fibres with bioactive compounds in their embodiment.Because of their application in medicine, the delivery systems are mainly discussed in terms offeatures such as biocompatibility and controllability. Other aspects, which are usually important intextiles, e.g. colour fastness and washability, are not included in this study.Practically the most important aspect of a drug delivery system is its biocompatibility, which nowadaysis defined in the following terms: “the ability of a material to perform with an appropriate host responsein a specific application”. Important elements included in biocompatibility are toxicity, carcinogenicityand related issues as mutagenicity (inducing changes in genetic material that are transmitted duringcell division) and teratogenicity (the ability or tendency to produce anomalies of formation). Forbiodegradable materials, not only should the parent material be harmless, but the degradationproducts as well. For most substances, the skin forms a natural barrier in entering the body, but within-vivo applications extra care should be taken in order to avoid the introduction of harmful substancesinto the body. A second aspect of biocompatibility is the product’s biostability and biodegradability.Depending on the application, a more or less biostable product is desirable. A general approach is thatin-vivo applications have to be biodegradable, removing the need for an extra operation to remove thematerial. For many ex-vivo applications, biostability is desirable, although ultimately biodegradabilitywould be beneficial, considering waste disposal. The interactions at the interfaces of the textilematerial and body tissue, e.g. the skin, form the third important biocompatibility aspect in developing aproper textile-based drug delivery system. Systems with excellent controllable delivery are of nointerest if they lead to considerable irritation of the skin at the same time.Another important aspect of a delivery system is its controllability. As mentioned before, in some of theconventional systems the risk of overdose is present. Using a slow-release delivery system, withwhich the drug can be delivered in a controlled way, might constitute a solution. Experiments will haveto be performed to bring system release patterns into view. Preferably, a system should becontrollable in such a way that release is possible within a certain range; that is, with any givensystem, different release patterns should be feasible responding to an individual patient’s need.Although difficult to quantify in the developmental stage, the material costs of a system are notirrelevant – there is no use in developing a system in which the benefits are cancelled out by thecosts. In developing medical applications, costs are often ‘allowed’ to rise, so long as a unique productwith a highly desired function is the result. However, in comparing different systems with virtually thesame goal, the cost aspect cannot be neglected; for this reason, a short discussion on this topic isincluded here. Related to the cost aspect is the production process. Conventional productiontechniques will in most cases be beneficial in comparison to specially developed new techniques;generally speaking, the more complicated the technique, the higher the costs. Therefore, differencesin system processing will be discussed and compared. Unfortunately , it will be difficult to make aquantitative analysis for many factors, and only qualitative considerations are given when comparingdifferent textile slow-release systems.

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Drug delivery systems

Cyclodextrins

Textiles bearing cyclodextrins consist of ordinary textile materials upon which cyclodextrin moleculeshave been fixed. Cyclodextrins are cyclic (α-1,4)-linked oligosaccharides, built from a number of D-glucose units. The generally most common forms are the so-called α-, β- and γ-cyclodextrins (seefigure 1 for an example). Because of the combination of a hydrophobic interior and a hydrophilicexterior, cyclodextrins can be useful components in the complexation of (hydrophobic) drugs. The ringsize of cyclodextrins can be varied since different cyclodextrins have cavities of a different size, butstill only selected groups of drug molecules that fit in the cavities can be used in complex formation. Itis stated that complex formation is largely independent of the chemical properties of the drug molecule[3], making the group of drugs that are compatible with a particular cyclodextrin quite large. This isunderlined by the different types of drugs that have been investigated in drug-cyclodextrin complexes,varying from neutral to ionic and from basic to acidic [4]. Furthermore, several modifications of theparent cyclodextrins are possible. The derivatives can be reactive (e.g. cyclodextrin with amonochlorotriazinyl (MCT) group), more hydrophilic (by means of hydrophilic side groups, such ashydroxypropyl and hydroxyethyl), less hydrophilic (by means of lipophilic side groups, such asethylhexyl glycidyl) or ionic (by means of ionic side groups, such as hydroxypropyl trimethylammonium chloride) [5].Cyclodextrins have been successfully immobilised upon textile fabrics. There are a number of ways toattach the molecule to the textile material, which can be classified into two main categories, physicaland chemical attachment. A specific example, which can be considered more as entrapment thanattachment, is when cyclodextrin is spun into the fibre. This can only be achieved with materialswhose fibres are made using melt or solution spinning, e.g. polyamide-6. Cooling the fibre leaving thespindle in a shock-wise manner causes the cyclodextrins to migrate to the surface [6], thus locatingthe cyclodextrins in the fibre’s outer sphere. This will keep the cyclodextrin cavities accessible to thedrug molecules. A second example concerns cyclodextrin derivatives bearing so-called ‘anchorgroups’. Anchor groups are able to penetrate textile fibres when the latter are in their amorphous state.These groups are mainly hydrophobic ‘tails’, such as alkyl or aryl groups [6], which fit excellently intothe fibre’s hydrophobic inner environment. The hydrophilic outer surface of the cyclodextrin willprevent complete penetration into the fibre; hence, the functional cavity remains accessible on thefibre’s surface [7]. Upon lowering the temperature (below Tg), the fibre polymers are restricted in theirmotion and the anchor groups are captivated, thus fixating the cyclodextrins [4, 6].When cyclodextrin derivatives are ionic in nature, the fixation with a textile fabric may be based onelectronic interactions. A specific example is the interaction of HPTMAC1-β-cyclodextrin withpolyacrylonitril fibres [4].The chemical fixation of cyclodextrins can be achieved by reaction of textile fibre functional groupswith the functional groups in the cyclodextrin. A straightforward example is the reaction of theaccessible cyclodextrin hydroxyl groups with (among others) hydroxyl, carboxyl, amide or other acidicor basic groups [6]. Cyclodextrin derivatives can have other functional groups, such as MCT, whichreacts through substitution of the chlorine atom by a negative polymer side group [4]. Anothercomparable fixation uses a third molecule as a kind of intermediate between fibre and cyclodextrin, forexample a polymer. Upon polymerisation, these compounds react with both the hydroxyl groups of thecyclodextrins and a textile fibre functional group, e.g. the hydroxyl group of cellulose. Furthermore,some network formation takes place, which leads to a combined fixation and entrapment of thecyclodextrins [6].The methods for treating the textile are thus quite simple. The method using anchor-bearingcyclodextrins is especially useful, since no fixation agent is needed, making it possible to useconventional textile treatment techniques and apparatus [4]. Furthermore, this method has virtually nolimitations with respect to the textile materials that can be used.Several tests [4, 8] have shown that the complexing power of cyclodextrins was maintained uponfixation. Hence, textiles treated with cyclodextrins can be used as drug carrying systems.Fixating cyclodextrins upon a textile material does not only alter the complexation power of thesystem. With derivatives containing large hydrophobic/lipophilic side groups, the diffusion time for awater droplet is increased, whereas hydrophilic groups have the opposite effect. The surfaceresistance is changed by the fixation of cyclodextrin derivatives. The surface resistance decreaseswhen increasing the amount of alkyl groups on the surface [4]. Another important change is the

1 HPTMAC: hydroxypropyl trimethyl ammonium chloride

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reactivity of treated fabrics, as the cyclodextrins introduce reactive hydroxyl groups to the textilesurface.

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Figure 1. Structure of β-cyclodextrin

Aza-crown ethers

An alternative to the attachment of cyclodextrins to textile materials is the attachment of aza-crownethers. The data on these kinds of systems are less detailed than for cyclodextrin systems, but still afew comments can be made. Aza-crown ethers are neutral, macrocyclic polyether molecules, in whichthe oxygen atoms are partially or completely replaced by nitrogen. In contrast with cyclodextrins,which have a 3D-structure, aza-crown ethers in their basic form are only 2D. The secondary aminegroups are possible substitution spots. The molecules are capable of forming stable complexes withmetal ions, in particular the so-called transition metals. Selectivity is governed by the (fixed) crown ringdiameter, the number of heteroatoms in the ring, the ion diameter and the charge density of the cation[9]. Aza-crown ethers can be fixed upon textile materials without loss of the crown ether’s complexingpower. This was tested by treating cotton, PET and PA-6.6 with aza-crown ether 22DD (ACE 22DD)),ACE (22TT), ACE (22TTp(NO2)2) and ACE (22TrTr) [9]. See figure 2 for examples of the differentstructural formulas.

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Figure 2. Several examples of the different structural formulas of some aza-crown ethers

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Fixation is achieved by treating the materials with a flowing ACE-solution in trichloromethane (ACE(22TrTr) in combination with cotton) or water (the other systems) and heating [9]. Again, two maintypes of fixation can be distinguished, namely a chemical reaction of side groups of the aza-crownether and the fibre, and the ‘anchoring’ of the aza-crown ethers through hydrophobic side groups.Increasing the temperature leads to an increased amount of fixed ligands, which is explained by thefacilitated penetration of the hydrophobic tails at elevated temperatures.

Fullerenes

Another way to fix macromolecules is by the use of fullerenes. Fullerenes are a so-called allotropicform of carbon; the material consists of only carbon atoms. A well-known example is C60, which ismore or less shaped like a football. Inclusions of helium and other metal ions in the fullerene innercavity have been reported. Furthermore, fullerenes themselves can act as a guest molecule incomplexation with macrocyclic ligands, such as cyclodextrins [10]. The fullerene groups can be usedas a starting point for self-assembling molecular layers, for example by combining them withcyclodextrins. Additionally, bound fullerenes are usually capable of reacting with other compounds.One possibility is a reaction with aza-crown ethers, which in their turn can bind other compounds andso on. In this way, layers with complexing capacity can be built [10]. Because of their olefinic,electrophilic character, fullerenes react in several addition reactions, e.g. in nucleophilic addition ofamines. This can be used to achieve the permanent fixation of fullerenes to polymers such as PET,PA-6.6 and wool, which contain amine elements.

Ion-exchange fibres

As the name suggests, ion-exchange fibres are capable of exchanging ions. The principle has beenknown for quite some time and these fibres are already used in many applications, e.g. in wastewatertreatment. Ion-exchangers bury either a positive or a negative electric charge, which is compensatedby (mobile) counterions of opposite polarity. Mobile ions of the same sign (co-ions) can also bepresent. In cationic fibres, the bound ionic groups are formed by e.g. –SO3

-, -COO-, -PO3- and -AsO3

-.Anionic groups are those such as –NH3

+, -NH2+, -NH+ and –S+. The principle of ion-exchange is based

on the electroneutrality requirement. The exchange is generally a diffusional process, sensitive toconcentration gradients, and the rate-determining step in ion exchange is the diffusion either within theexchanger itself or in the so-called diffusion boundary layer. Usually ion-exchangers take up somecounterions in preference to others. This fact can be used in controlling the exchange [11]. Drugstability during storage improves upon bonding them in ion-exchange fibres.The drugs act as the mobile counterion. They can be released by ions in bodily fluids, though thismight disturb the homeostasis. Furthermore, in ex-vivo applications, the amount of such ions willprobably be too low to achieve sufficient drug release. Hence, a co-solution of a salt, such as sodiumchloride or sodium phosphate [12], is used. The sodium ions will replace the drug ions. and the latterwill combine with (in this case) the chloride or phosphate ions. The salt can be encompassed in a gel(based for example on gelatin, agar or polyvinyl alcohol), which is then brought into contact with thetextile fibre loaded with the drug. The salt will diffuse through the gel and the fibre, and thus releasethe drug [12]. An interesting application may be to use ion-exchange fibres for the regulated in-vivodelivery of insulin, in order to treat diabetes mellitus [13, 14]. In literature, chemically bonded drugs arementioned as a variation on ionic drug-ionic fibre interaction [14].Ion-exchange fibres suitable for drug delivery are already commercially available. Examples are theso-called Smopex® fibres, which consisting of a polyethylene backbone grafted with other polymers,e.g. poly(styrenesulphonic acid) (Smopex®-101) polyacrylic acid (Smopex®-102) or polyamide(Smopex®-108) [2, 11]. Besides using the commercially available ion-exchange fibres, it is alsopossible to graft ion-exchange groups to a (textile) fibre. Fibres suitable for this purpose includecellulosics and wool, but also synthetic fibres like polyethylene, polystyrene, polyacrylonitril, polyamideand carbon fibres [12]. The amount of functional groups grafted onto the fibres affects its loadingcapacity.

Hollow fibres

Hollow fibre systems can be seen as small tubes which can be filled with a drug. The fibre wall usuallyconsists of a permeable membrane that can be used in controlling drug release. The fibres areadvantageous in two ways, as they have a high surface area to volume ratio and a high loading

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flexibility. The system can comprise hollow tubes filled with a liquid drug or a drug solution [15].Another possible form is a hollow fibre in combination with (an) ion-exchange resin(s) [16]. Also, drugcrystals dispersed in a polymer core [17] can be used. In yet another variety, drugs are dissolved insuch a core [17]. The systems in which the drug is bound into a polymer are prepared by mixing thedrugs with a polymer material, in order to give a drug-loaded core granulate. If desired, differentdrug/polymer granulates can be mixed. The mixture is heated in order to melt the polymer; the drug isdissolved in the polymer. After cooling, the mixture is granulated again. These granulates are used inco-extrusion together with granulates of the polymer which is to form the fibre membrane. Bothgranulates are molten (but not mixed), and by accurately controlling the two polymer flows through aspinneret, a coaxial fibre combining the polymer core and the fibre membrane is formed [17]. Whendrug crystals are desired, the melting of the polymer-drug combination before co-extrusion is skipped.

Nanoparticles

In the treatment of textile with nanoparticles that contain a functional agent (which can be a drug), thenanoparticles are permanently fixed on a textile fabric through chemical bonds, either by directreaction of a particle side group and the textile, or by means of a linker molecule. The nanoparticleencapsulation is used to circumvent possible alterations and loss of functionality of the agent, whichcould be the case in a direct reaction between the agent and the textile. However, linkers for directchemical attachment and also useful in controlled release are difficult to engineer, and must bedeveloped for the various agents individually [18].The nanoparticles consist of a drug, either surrounded by a synthetic, polymer shell or containedwithin a synthetic, 3D polymer matrix, both micrometric to nanometric in size. Encapsulation can beachieved by several methods, e.g. interfacial polymerisation, microemulsion polymerisation,precipitation polymerisation and diffusion. In general, the drug is brought into contact with a set ofmonomers, oligomers or polymers. These assemble around the payload; polymerisation will give thefinal particles. An alternative way is to prepare the nanoparticle in the absence of the drugs, which areabsorbed by the nanoparticles following afterwards [18].A wide range of applicable monomers, oligomers and polymers is available. Some very usefulsystems are those containing amine, hydroxyl or sulph-hydryl monomers or polymers combined withamine-, hydroxyl- or sulphhydryl-reactive monomers or polymers. Both hydrophobic and hydrophilicmonomers can be used; the choice depends on the drugs to be encapsulated [18]. As an extra option,systems can be copolymerised with soft or rubbery monomers or polymers (e.g. acrylates ormethacrylates), to improve wearing properties such as ‘skin softness’ and wrinkle and abrasionresistance [18]. The monomer or polymer systems used contain at least one component able to reactwith a textile material even after polymerisation. Wool and other animal fibres contain hydroxyls,amines, carboxylates and thiols. Synthetic fibres usually have a limited number of reactive groups.The same holds for cellulose and its derivatives as well as other plant materials, which have to reactthrough their hydroxyl groups. In order to increase the possible particle-textile combinations, abifunctional molecule can be used, for example to link an amine-reactive particle with cellulose (whichcontains no amine groups) [18]. For particle fixation, the textile material is exposed to a solution,dispersion or emulsion of the textile-reactive particles, by conventional methods such as soaking,dipping, spraying, fluid-flow or padding [18]. A catalyst may be present in the medium. The actualfixation takes place in the curing stage, which can take place while the textile is still in contact with theparticle solution (dispersion, emulsion), but preferably after the drying stage. In the case of using alinker molecule, the textile material may first be treated with the linker and subsequently with theparticle solution [18]. The contact time can vary widely, from seconds to days, as can temperaturesand pressures [18].

Drugs incorporated in fibres

Another approach in creating textile drug-delivery systems is processing the drug in the fibre’spreparation stage. With the hollow fibres, there was still a distinct separation into fibre (the membranewall) and drug (the core). Yet another way of incorporating drugs into fibres is to suspend or dissolve abioactive compound (in particular a drug) into the polymer solution used to produce the fibres. If abioactive compound is to be incorporated within or inside the polymer fibre, polymer selection is basedupon the solubility of the drug in the polymer solution. If the drug is to be located between the fibres,this is of no concern. Instead, the drug can be suspended in the polymer solution before the actualspinning. The spinning will give nonwoven meshes of nano- and micron scale fibres. These fibres canbe processed into matrices, linear assemblies and braided or woven structures, or be used in film

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coating. Fibres can be spun from any polymer which can be dissolved in a solvent. This includes non-degradable polymers such as polyethylene, polyurethanes and polyethylene vinyl acetate copolymers,but also biodegradable polymers such as poly(lactic acid), poly(glycolic acid), poly(orthoesters) andpoly(phosphazenes) [19]. An interesting development related to this kind of system is the synthesis ofa biodegradable polymer with a drug incorporated into the polymer backbone. Upon degradation of thepolymer, the drug is released again. It has been shown that polymers can be developed which aremore easily degraded in the presence of certain enzymes, e.g. enzymes highly presence at infectionspots. Hence, the drug release would be more or less ‘triggered’ by the infection (in this case) [20]. Aserious drawback reported in the literature is the system’s low efficiency. This can be explained by thefact that upon degradation of the polymer, the degrading ‘scissions’ are not always made perfectly ateach junction of drug and polymer, and a number of non-functional rest products are formed [20].These kinds of polymers have not yet been tested for processing into fibres and textile materials, but itmight be an interesting option to experiment on this point. When doing so, it is not necessary torestrain oneself to drug-containing polymers only; for improvement of mechanical properties, forexample, combinations with other (biodegradable) polymers can be made.

Toxicity and carcinogenicity

Cyclodextrin-bearing textiles can be considered as not harmful. Conventional textile materials canform the basis of the system, and the only harm could lie in the cyclodextrins. Detailed studies of thetoxicity, mutagenicity, teratogenicity and carcinogenicity of some cyclodextrins and their derivativeshave been made. These substances were potentially harmful only in extremely high concentrations,and no acute toxicity has been observed [7]. More detailed information on specific cyclodextrins canbe found in the literature [21]. In general, they are considered to be non-toxic [22].For aza-crown ethers, little specific data on toxicity and carcinogenicity has been found. It has beenstated that aza-crown ethers are less toxic than their crown ether equivalents, due to the reducedinfluence on potassium leakage into and sodium leakage out of cells. Complexed ligands are muchless toxic than uncomplexed ones. Besides, as aza-crown macrocycles have been investigated formedical purposes for a long time, e.g. for their use in antitumour treatment, in treatment of kidneystones and even as a drug element, it can be assumed that their toxicity and carcinogenicity isacceptable with respect to medical limits [23]. More specific data (although very limited) on the aza-crown ether used in the specific example described above (ACE (22DD)) can be found on theInternet2. Upon exposure, no harmful effects have been indicated in the information available. Thematerial is not listed as being carcinogenic.For fullerene-bearing textiles, it could be stated that these materials are not highly toxic, since freefullerenes are applied in other medical fields as well, implying a harmless effect of this group [24, 25].In literature found on ion-exchange fibres, no comments are made on toxicity. As the polymer basematerials are formed by common, non-toxic and non-carcinogenic materials, toxicity andcarcinogenicity would have to stem from the ion groups attached to the polymer backbones. As thegroups are bound to the polymer, no harm is to be expected from free ionic groups. Furthermore, theion groups are neutralised by a suitable counterion ‘at all times’, be it either a drug or an electrolyteion, hence the possible negative effect is cancelled. For in-vivo applications, the ion exchange fibremight present problems when it disturbs the homeostasis. Confining the use of ion-exchange fibres toex-vivo applications, the subject of toxicity and such is practically irrelevant; if electroneutrality ismaintained at all time, in-vivo applications will not give rise to problems either.In drug-loaded hollow fibres, the material used for the hollow fibre matrix is generally a conventionalmaterial known to be non-toxic or non-carcinogenic, like polyurethane, nylon or polyethylenevinylacetate copolymers [15-17]. The possible toxic effect thus lies in the drug inside the hollow fibre.As drugs in high doses might have a toxic effect, it is crucial that the release patterns of the hollowfibres do not give rise to such doses. Furthermore, the way the drug is incorporated in the fibre isimportant. It is important to characterise their filling, because of possible biodegradability especially,but also with regard to fibre damage..For textile materials treated with nanoparticles, the base materials are common and well-knowntextiles of both natural and synthetic origin. Hence, no toxicity is to be expected from them. Byselecting the appropriate polymer materials for encapsulating drugs and such, no toxicity is to beexpected thereof either. As nanoparticles are covalently bounded to the textile materials, they are thus

2 source: http://www.emscience.com/catalogs

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immobilised in possible in-vivo applications; no harm will be caused by particles wanderingthroughout the body.For drug-loaded polymers, again the toxicity and carcinogenicity are determined by the choice of thepolymeric material. In the case of non-degradable polymers, no problems are to be expected, but forbiodegradable polymers, the degradation products should be non-toxic. Using materials such aspoly(glycolic acid), which have been thoroughly investigated on aspects such as toxicity, no problemsare to be expected for biodegradable polymers.

Biostability and biodegradability

For textile materials bearing cyclodextrins, the choice of the base material is decisive when concerningbiostability and biodegradability. Materials like cotton or wool are fairly biostable, though notindefinitely [18]. In normal wear, body substances do not immediately damage them; mechanicalforces and things like weather, UV radiation and attack by microorganisms are the principal cause ofany damage. The materials’ lifetime can be enhanced by treatment of the finished materials to requireantibacterial, anti-insect or fungicidal effects, among others. Ultimately the materials will deteriorate,and in that sense they are biodegradable. Synthetic materials (e.g. nylons, poly(ethylene terephtalate)(PET)) are more biostable in that respect. The cyclodextrins themselves are readily biodegradable[22].In literature on the fixing of aza-crown ethers on textile materials [9], no comments were made onchanges in biodegradability. However, it is rather inappropriate to assume that introducing the aza-crown ethers did not lead to any drastic changes in the biostability and biodegradability. For aza-crownethers in combination with silver ions, for example, the antimicrobial effects of the loaded groups mightbe considered as enhancing long-term biostability. (Ultimate) biodegradability depends, again, on thechoice of the base material.In literature concerning fullerene-treated textile material, no specific comments have been made onbiodegradability or biostability. As common materials form the base, these will mainly govern thebiodegradation pattern. As with aza-crown ethers, the fullerene groups can provide antimicrobialeffects (e.g. by complexation of silver ions), implying increased biostability.For ion exchange fibres, biostability and biodegradability is largely influenced by the choice of thebase material. One such commercial available system is the Smopex® fibres. These materials, or atleast their polyethylene backbones, are non-degradable. Also, traditional textile materials such as wooland cotton can be used – the biodegradability of these materials has been discussed before. Thelarge amount of electrically charged groups in the fibre is bound to have an influence on biostabilityand biodegradability, although nothing is mentioned in the literature cited. It can easily be understoodthat a change in the fibre‘s equilibrium situation will lead to a reactive system, more susceptible tophenomena such as degradation. However, especially in ex-vivo applications such as textilecoverings, there is unlikely to be any large disturbance of the equilibrium other than the desired one,which causes the release of the drug.The biostability and biodegradability of a hollow fibre system depends on the material chosen for thefibre wall. Of course, with a non-degradable material such as polyurethane, the fibre remains intact.For some applications, especially in-vivo, biodegradability is desired, as it takes away the necessity tosurgically remove the system. In such cases, biodegradable materials such as poly(lactic acid) orpoly(glycolic acid) can be used. The choice of the material is very important, as biodegradation willinterfere with the release rate.With nanoparticles, the biostability and biodegradability of the system is primarily determined by thechoice of the base material. As common textile materials form this, the same biostability andbiodegradability considerations hold as for cyclodextrin treated materials (among others). For in-vivoapplications, suitable materials have to be chosen, if they are desired to be biodegradable. Thepolymer material used for encapsulating the drug is not really important with respect to biostability orbiodegradability of the systems as a whole. Practically all polymers are suitable for encapsulation,though the choice of polymer is of influence in the release pattern of the particle [18]. When desired, abiodegradable material can be chosen so that degradation will (partially) control the release of theparticles’ contents. A nanoparticle treatment is not limited to giving the textile material a drug releasingcapacity. By encapsulation of appropriate agents, for example anti-fungal or anti-insect, biostabilityand non-degradability can be improved [18].The biodegradability and biostability of the drug-loaded fibres is determined by use of the polymer.Again, biostability is guaranteed when using well-known polymer materials such as polyethylene orpolyurethane. Though nothing has been mentioned in the literature, it is of course interesting to

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investigate whether solubilising the drug into the polymer has an effect on polymer properties, one ofwhich is biostability. For some polymer fibre systems, biostability is undesirable, as the release of thedrugs depends upon degradation. Hence, the material is designed to have a fair biodegradation rate,e.g. by introduction of a large amount of ester linkages. Some control over the degradation rate can beachieved by choosing the appropriate monomers.

Interface reactions

For cyclodextrin textiles, some tests are performed which consider irritating or sensitising effects [7]. Itshould be borne in mind that there are several different cyclodextrins and derivatives, not all of whichhave yet been tested with regard to these effects. With aza-crown ethers, unfortunately no specificdata was found on this aspect. For fullerenes, again, no comments were made in the literature. Basedupon safety data, one could expect some problems, as C60 is marked as being ‘irritating’3, and contactwith skin and eyes should be avoided. It is unclear how fixing and possible further complexation altersthis behaviour.For ion-exchange fibres, only in-vitro (in-the-lab) tests have been performed so far, using humancadaver skin [11], therefore no real statement can be made regarding possible interface reactions. It isquestionable whether the large amount of charged groups in the system might give rise to phenomenasuch as skin irritation when the equilibrium is disturbed. As the latter is not likely to happen (inpreparing ion-exchange fibres, the fibres are washed with water a few times without leading to anybuild-up of charge), no problems should be expected here.With hollow fibres, irritation would stem from the choice of the fibre wall material. By choosing well-known fibres, which are known not to cause bodily responses and to be comfortable to wear, irritationis not an issue.For textiles treated with nanoparticles, the textile materials themselves are unlikely to cause anyundesired effects, as they are common materials which people are used to. For drug encapsulation,polymers with known, advantageous properties regarding interactions between the material and thehuman tissue will have to be chosen. As the list of useful polymers is almost infinite, a suitable solutionfor almost any situation is to be found [18].As far as interface reactions are concerned, the drug-loaded fibres will present no problems as long aspolymers are chosen that are considered to be ‘safe’, such as polyethylene. Again, it might beinteresting to investigate the effect of drug solubilisation on polymer properties: one possibility wouldbe the occurrence of surface modifications, which could be disadvantageous in respect of interfacereactions. For biodegradable fibres, it is not only the fibre that might cause interface reactions, but alsothe degradation products.

Controllability

The mechanism of drug release from cyclodextrin complexes has been investigated in severalexperiments. An initial difficulty in making remarks on controllability is that practically everycyclodextrin derivative has its own release pattern, as do combinations of cyclodextrins with differentdrugs. This is due to the fact that the interactions governing the complexation strengths vary in everycase (as expressed by k1/k-1 in the formula below). The drug-cyclodextrin complexation anddecomplexation (release) is an equilibrium process of the type:

D1+CD D1-CDk1

k-1

D1+CD D1-CDk1

k-1

where D1 is the drug, CD the cyclodextrin and D1CD the drug-cyclodextrin complex. It is stated that forweakly complexed drugs, dilution is controlling decomplexation, as it shifts the equilibrium. For morestrongly bound drugs in drug-cyclodextrin complexes, competitive displacement and protein drugbinding are important as well; the former shifting the equilibrium by decreasing the available amount offree cyclodextrin, the latter by decreasing the available amount of the free drug [26]. The statementsabove are based upon experiments dealing with non-fixed cyclodextrins in oral delivery systems. Asthe fixation of cyclodextrins did not affect their complexing power, it can be reasoned that the release

3 source: http://www.chemexper.com/

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pattern is not influenced by the fixation either. However, a more detailed study on this topic isdesirable. In literature, some experiments in changing the release pattern have been reported. Again,these concern non-fixed cyclodextrins. Two examples:

• Cyclodextrins can be used to overcome problems in drug solubilisation, e.g. water-insoluble drugscan be solubilised. Release is then based on changing the environment, for example fromaqueous to lipophilic, and can be regarded as a ‘triggered’ release. Once triggered, the release isimmediate and without delay [5].

• Drug release can be delayed by using pH-sensitive systems, e.g. systems that are less soluble inwater at low pH, but soluble in neutral or alkaline regions due to the ionisation of an acidic group.In oral administration, this means that drug release can be delayed until the complexes havepassed the stomach and reached the smaller intestine [5].

Unfortunately, no general rules concerning drug release can be derived from this kind of information. Itcan be stated that it is a question of ‘trial and error’ – that is, for a given situation, a particular complexhas to be found which will give the desired pattern. For ex-vivo applications, it must therefore beconcluded that once a combination of drug and cyclodextrin is chosen, the release pattern is fairly wellset, unless a multi-layer system is created.For aza-crown ether textiles, few comments can be made regarding the controllability of the system,as no real delivery takes place. It is however essential to investigate the possibility of the migration ofthe complexed ions (which was suggested in antimicrobial tests), and its effect on phenomena such asinterface reactions. For fullerene systems, the same statement applies.With ion-exchange fibres, the release pattern can be changed in several ways. An example: toactivate Smopex®

fibres, i.e. to create ionic groups, fibres were treated with NaCl. When a mixture ofNaCl and NaOH was used, it appeared that drug binding increased, though the fraction of the drugcontent released was the same. Hence, increased drug release can be achieved by appropriateactivation, though this leads to relatively greater drug wastage [11]. The drug release increased with adecrease in electrolyte concentration (the ‘helper’), which can be explained by considering the drugequilibrium. It must be emphasised that the decreasing electrolyte concentration is a result ofincreased external volume: when the same amount of electrolyte is used, the external volume will bemuch higher in the case of lower concentrations. Hence, equilibrium is shifted towards release.However, the decreased electrolyte concentration increases the electrostatic affinity between the drugand the fibre. Apparently, the tendency to re-establish the drug equilibrium is the predominant effect.The opposite situation would be observed if the same external volume would be used for the differentelectrolyte concentrations, because in this case the shift in equilibrium would not be that great, and theaffinity effect will be overriding [11]. Changes in the electrolyte can help to increase drug release.When CaCl2 was used in combination with NaCl instead of NaCl alone, drug release is increased dueto the stronger tendency of Ca2+ to bind to the ion exchange groups. This effect appears to be pH-dependent [11]. To summarise, drug release can be controlled to some extent by choosing theappropriate fibre-drug combination and by changes in the electrolyte solution, concentration, andcomposition as well as pH. In order to extend control over the release pattern of the drug from thefibre, so-called iontophoresis can be used. This method, in which the fibres are placed in an electriccell and subjected to an electric current, can be useful in releasing drugs that are not released in apassive way [2]. Furthermore, forced exchange can be used to overcome the large biologicalvariations that can exist between patients. The strength of current can be used in controlling therelease rate.For hollow fibres, the fibre membrane usually controls the release. Several types of polymeric-controlled release systems have been developed for commercial applications. These can becategorised in three basic types, regarding the rate-controlling mechanism: diffusion-controlled,chemical reaction-controlled and solvent activation-controlled. Most control systems use one ore moreof these mechanisms. Much attention has been paid to the mathematic modelling of controlled releasefrom hollow fibres [27-29]. These mathematical treatments are beyond the scope of this review. Withthe drug present in the crystal state, the concentration of the dissolved drugs is determined by itssaturation solubility. In this case, the release rate can be controlled by the thickness and permeabilityof the fibre membrane. As a consequence, this concept can only be used to control the release of asingle drug [16]. When the release of more than one drug is to be controlled, it is necessary todissolve the drugs completely. In this way, the release can be controlled independently by theconcentration of each drug and by the membrane characteristics. The release is then influenced bythe solubility and diffusion coefficient of a drug in the core polymer [17]. If a constant release isdesired, the permeability of the bulk polymer (the core) for a specific drug should be much higher thanthe membrane permeability. Thus, by choosing the appropriate membrane material and thickness, a

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specific release pattern can be established. However, once this is set, no further means of controlremain. When release is not only diffusion-controlled, changes in the release environment (e.g.changes in solvent composition) can be used to control drug release.With nanoparticles, the architecture of the particle shell or matrix can be formulated and fine-tuned toexhibit the controlled release of its contents, ranging from constant but prolonged release to zerorelease. The particle can be formulated with an almost infinite degree of designed characteristics viakey structural features, such as cross-linking density, hydrophilic-hydrophobic balance of thecopolymer units and the stiffness of the polymer network. Furthermore, erodible or biodegradableparticles can be used to combine the release mechanisms of diffusion and erosion. In addition, theparticles can be designed to respond to different stimuli to alter the rate of release. The polymers canbe induced to undergo a distinct thermodynamic transition by the adjustment of any of a number ofenvironmental parameters, e.g. pH, temperature, ionic strength, co-solvent composition, pressure orelectric field. Examples are polymers that, based on the lower critical solution temperature transition,drastically cut off release when exposed to higher temperatures [18].With fibres which incorporate the drug within, some control over drug release can be introduced byvarying the choice of polymer used in the fibre (influencing drug diffusion), the diameter of thepolymeric fibres (controlling diffusion distance), the concentration of polymer used in the fibre(influencing fibre structure) and the amount of drug loaded in the fibre (influencing concentrationgradients) and biodegradability of the polymer (fast biodegradation enhancing drug release). Ofcourse, these variables only apply to situations where the drug is located within the polymer fibre. Thedrug-loaded fibres can be combined with non-loaded fibres, either biodegradable or non-degradable,which can be used to change the distance over which a drug has to diffuse before it is set free into thebody/onto the skin (among other factors), which hence constitutes another means of controlling drugrelease [19]. A release pattern is fixed once the fibre is prepared. As a final remark, it can be said thatcreating a proper release system is more or less a question of trial and error, as various drugsinterfere differently with various polymers.

Material costs

For the textile materials treated with cyclodextrins, the base materials can be common textiles such ascotton, cellulosic or synthetic fibres such as PET. There is no need for pre-treatment of thesematerials, and hence, in comparing the system with other systems, the material costs are mainlydetermined by the cyclodextrins. Research in the cyclodextrin area has grown, leading to numerouspublications and patents [7]. Biotechnological advancements have led to great improvements incyclodextrin production, lowering production costs [3]. This phrasing can be used to assume thatcyclodextrins, at least the parent ones (α-, β- and γ-dextrin) will have acceptable costs. Besides – andthis should be emphasised – at least for ex-vivo, non-biodegradable materials, the cyclodextrins canbe reloaded and hence the material can be recycled. In Table 1 a rough idea of the market prices ofcyclodextrins is given:

Table 1. Market prices of different cyclodextrins (2002)

Natural Cyclodextrins Pricesa

α-cyclodextrin 99% 5g €18.48β-cyclodextrin 99% 5g €9.24γ-cyclodextrin 99% 5g €130.90

Neutral Modified Cyclodextrinsβ-dimethyl cyclodextrin 5g €150.92β-trimethyl cyclodextrin 5g €831.60

β-2-hydroxypropyl cyclodextrin 5g €150.92Ionic Modified Cyclodextrins

β-cyclodextrin phosphate 2.5g €485.10β-carboxy methyl cyclodextrin 5g €121.66

β-amino cyclodextrin 5g €2710.40

(source: http://www.capital-hplc.co.uk/cdex.htm),aOriginal prices in British pounds; exchange rate taken as £1 =€1.54

As can be seen in this table, when moving from unmodified to modified cyclodextrins, the pricesrapidly increase. Unfortunately, for fixation upon textile materials using common textile-finishing

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techniques, modification is a necessity. For medical applications, these costs might be acceptable.One should further bear in mind that the quantities mentioned in Table 1 are lab-scale quantities. Forother applications, e.g. delivery of fragrances4, the prices will have to drop. Thus, the desire to usecyclodextrins for other than medical applications might lead to even lower prices, due to furtherdevelopment and increased production, with large quantity sales.Because of the relative cheapness of the base materials, the material costs of aza-crown ether treatedtextiles are mainly determined by the prices of the aza-crown ethers. As an indication, the market priceof the aza-crown ethers, ACE (22) and ACE (22DD), used in literature can be taken: €53 and €212 forone gram, respectively5. This is considerably higher than the prices of cyclodextrin; besides, only anti-microbial activity without drug delivery capacity is achieved, making the material even more expensivein relative terms.For fullerenes, again the main cost-determining factor is the fullerenes themselves. Some indicationscan be found on the Internet: market prices vary from €1756 to €2126 for 5g C60, 99.5% pure and€3047 to €9017 for 5g C60, ultra pure (>99.95%). Furthermore, in the fixation process γ-cyclodextrinsturned out to be a useful solubilising agent, but as was shown, these materials are not very cheap.In ion-exchange fibre systems, the textile material itself is the drug carrier. As mentioned, several ion-exchange fibres are available, e.g. the Smopex® range, based on grafted polyethylene. It is to beexpected that these specialty fibres exceed the ordinary textiles in costs. However ordinary textilessuch as cotton, can also be used to create exchange fibres. Besides, no extra carrier group is needed:once it is spun, the fibre is capable of carrying drugs, albeit that it has to be activated in order to createionic groups. As the latter can be achieved by fairly simple salt solutions, this will not be of especialrelevance when considering costs. The necessity for a release ‘helper’ might be disadvantageous,since this demands a different textile setup (e.g. the need for an extra electrolyte reservoir).For drug-loaded hollow fibres, the costs can be divided. Of course, there are the costs of the fibreitself. It can be reasoned that producing hollow fibres demands more sophisticated techniques, whichwill show in the costs. Strictly speaking, this falls within the aspect of the manufacturing process andcosts, and should not be taken into account here. As the fibre material can consist of commonpolymers, high costs are not to be expected thereof. As for the filling, it depends on how the drug is tobe bound inside the fibre. Some alternatives, such as a polymer gel or crystallisation in combinationwith other substances, will give rise to additional material costs.With nanoparticle-treated textiles, a great advantage concerning material costs is the ability to usecommon textiles as base materials, and thus, again, no great impact on material costs is to beexpectedas a result. For nanoparticle synthesis, a broad range of materials is available, including thecommon ones. Not all of them are qualified as bulk polymers [18]. For specific polymer coatings, withspecific release properties, costs can therefore rise.The material costs in creating drug-loaded fibres are determined by the choice of the polymer. Ascommon polymers such as polyethylene can be used, systems do not necessarily have to beexpensive. When considering the material costs for the biodegradable polymers in which the drug is tobe incorporated in the main chain, the drug itself should not be taken into account, as was not done inthe other systems. Hence, only the other polymer ingredients, i.e. the monomers, basically form thematerial costs. Whether the system is costly or not thus depends on whether the monomers are bulk(and hence ‘cheap’) or not.

Manufacturing process

A major advantage immediately follows from the way the cyclodextrin-textile system is prepared. Theattachment of the cyclodextrin groups is achieved by relatively simple and well-developed textiletreatment techniques [8]. Furthermore, which may be even more important, it is possible to treat analready fabricated piece of cloth [4, 6]. Hence, the manufacture of the textile material can beseparated from the actual system formation, offering the possibility of specialisation without having todeal with the problems concerned with textile production. A second advantage of the possibility oftreating finished textiles is that it can be guaranteed that the cyclodextrin groups are mainly attachedto the textile surface that will form the interface with (for example) the skin. Hence, the majority of theoriginal drug-loading capacity is maintained, in contrast with preparing cloth from treated fibres. As a

4 which can also be achieved with cyclodextrin treated textiles5 source: http://www.emscience.com/catalogs - original price in dollars; exchange rate taken $1 = €1.066 source: http://www.mtr-ltd.com/pricelist.htm - - original price in dollars, exchange rate taken $1 = €1.067 source: http://www.sesres.com/FullerenesPrices.asp - original price in dollars, exchange rate taken $1 = €1.06

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final remark considering manufacture, it can be stated that only one textile treatment is necessary tocreate a feasible, drug-loadable system; this in comparison with the traditional multi-phase systems, inwhich separate layers have to be created [1]. For aza-crown ether textiles, the comments made abovealso apply.For fullerene-treated textiles, the manufacturing process is, again, relatively simple, though techniquesdifferent from the conventional ones for textile treatment are used, which can be seen as adisadvantage. Besides, the fixation process takes more time in the case of fullerenes compared forexample to cyclodextrins. In the examples, for cyclodextrins, preparation times were in the order ofminutes to a few hours [4, 6], whereas in the case of fullerenes, fixation took a day or even more [10].With ion-exchange fibres, the activation step can also be considered as being a disadvantage in thefabrication process, when the latter is considered as being the complete processleading to a systemready for drug loading. Nevertheless, as ion-exchange fibres are used in applications other thanmedical, e.g. wastewater treatment, removing metal out of liquors and such, it can be stated that theproduction of such fibres has passed the developmental stage and is now commercially attractive.This is stressed by the use of the ion exchange fibres found in the literature, which were commerciallyavailable.The fabrication of many types of hollow fibres has developed in such a way that no great difficultiesand hence no extreme costs are nowadays to be expected thereof. However, the hollow fibres have agreat disadvantage in comparison with the other systems discussed so far, namely the coupling ofloading the fibre to the manufacture in some cases, e.g. in the case of the drug crystals in the polymercore. This calls for specialisation, in the sense that those producing the fibres will also have to have arange of different drugs at their disposal.With nanoparticle treatment, a great advantage is that it is applicable to both fibres and finished goods[18]. Thus, as with cyclodextrins, the specific treatment in order to get useful drug delivery systemscan be decoupled from the fabric production. Furthermore, the application of the nanoparticles to thesystem can be achieved by known textile treatment techniques, which is also advantageous.With fibres with drugs in their embodiment, the fabrication costs are of no real interest, as thetechniques used are fairly simple. A far more interesting point is the fact that the drug is incorporatedinto the fibre while processing the fibre. As was mentioned with the hollow fibre systems, this is ratherdisadvantageous, as it calls for the availability of both polymers and various drugs on one productionlocation.

System comparison

In the foregoing paragraphs, a number of textile delivery systems are discussed. As to be expected,some of them look more promising than others. Moreover, further development is desirable. In thisparagraph, the systems’ “weak spots” are discussed again, but now in comparison with other systems.Concerning the aspect of toxicity, carcinogenicity and such, no real distinction is to be made betweenthe systems, at least not based on the literature cited. The real toxicity stems from the drugs usedthemselves; this should not be taken into account, as it is virtually the same for all cases. It has beenmentioned that especially in the case of the aza-crown ethers and fullerenes, additional research isdesirable.For biodegradability and biostability, the same statement holds. On the other hand, based onliterature, the combination of cyclodextrins, aza-crown ethers and fullerenes with textile materials is tobe applied more in the field of ex-vivo than in-vivo delivery systems. This is underlined by the textilebase materials used, which are all representatives of those materials used in common clothing. Inorder to take advantage of the ability of system regeneration, in-vivo applications are even more ‘outof the picture’. Biodegradable systems, which are more interesting for in-vivo applications, have notyet been explored. The same goes for nanoparticle treatment, which has been rather restricted tocommon textiles. As for the ion-exchange fibres, it is to be expected that these systems will consistmainly of non-degradable fibres, when considering the treatments these materials are subjected to.However, it is interesting to explore the concept of combining biodegradable textile materials withcyclodextrins and nanoparticles, especially for in-vivo use. As an example: can the same fixatingprinciples and treatment processes be used in combination with biodegradable polymers?In-vivo biodegradable applications are more likely to come into view when using hollow fibre systems,drug-loaded polymers or polymers containing a drug in their backbone.As for the interface reactions, it can be stated that the data in the literature cited is insufficient to makesubstantial comments, and no real comparison can be made here. It can be stated that at least the

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cyclodextrin, nanoparticle, hollow-fibre system and some of the drug-loaded fibre systems can befreed of irritating effects. For the other systems, interface reaction experiments are desirable.As for material costs, the most interesting systems will probably be those using the common textilematerials as its base, such as the cyclodextrin system and the nanoparticle system. To some extent,the ion exchange system can be mentioned here too, as it was shown that it is possible to graftcommon textile materials with ion-exchange groups.In fabrication, the cyclodextrin and nanoparticle systems will also be economically of most interest, asthey can be prepared by using common textile-treatment techniques. As no further information wasfound on the grafting of textiles in order to get ion exchange fibres, no real comments can be made onthis point. It is interesting, though, to have a further look at these systems, because ion exchangefibres are promising with respect to other aspects as well, especially controllability.Since little distinction could be made between the systems by considering all aspects exceptcontrollability, the latter can be considered to be the most important aspect. As mentioned, for mostsystems release patterns can be controlled in their preparation, but once prepared, the release patternis fixed. The only two real exceptions are the ion-exchange fibres and the nanoparticle systems.These systems could be controlled afterwards by means of such factors as electrolyte composition (incase of the exchange fibres) or pH. The most interesting systems at this point would therefore be theion-exchange fibre system and the nanoparticle-treated textile systems.

Acknowledgements

The Textile Technology Group at the University of Twente acknowledges the financial support of theFoundation Technology of Structured Materials in the Netherlands and of the Dutch Ministry ofEconomic Affairs.

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